Abstract
Congenital cytomegalovirus (cCMV) infection is the most common congenital infection and the leading acquired cause of developmental disabilities and sensorineural deafness, yet a reliable assessment of the infection burden is lacking. To estimate the birth prevalence of cCMV in low- and middle-income countries (LMICs) and high-income countries (HICs), characterize the rate by screening methods, and delineate associated risk factors of the infection. MEDLINE/PubMed, Scopus, and Cochrane Database of Systematic Reviews databases were searched from January 1, 1960, to March 1, 2021, and a total of 1322 studies were identified. Studies that provided data on the prevalence of cCMV derived from universal screening of infants younger than 3 weeks were included. Targeted screening studies were excluded. Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Extraction was performed independently by 3 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. Random-effects meta-analysis was undertaken. Metaregression was conducted to evaluate the association of sociodemographic characteristics, maternal seroprevalence, population-level HIV prevalence, and screening methods with the prevalence of cCMV. Birth prevalence of cCMV ascertained through universal screening of infants younger than 3 weeks for CMV from urine, saliva, or blood samples. Seventy-seven studies comprising 515 646 infants met the inclusion criteria from countries representative of each World Bank income level. The estimated pooled overall prevalence of cCMV was 0.67% (95% CI, 0.54%-0.83%). The pooled birth prevalence of cCMV was 3-fold greater in LMICs (1.42%; 95% CI, 0.97%-2.08%; n = 23 studies) than in HICs (0.48%; 95% CI, 0.40%-0.59%, n = 54 studies). Screening methods with blood samples demonstrated lower rates of cCMV than urine or saliva samples (odds ratio [OR], 0.38; 95% CI, 0.23-0.66). Higher maternal CMV seroprevalence (OR, 1.19; 95% CI, 1.11-1.28), higher population-level HIV prevalence (OR, 1.22; 95% CI, 1.05-1.40), lower socioeconomic status (OR, 3.03; 95% CI, 2.05-4.47), and younger mean maternal age (OR, 0.85; 95% CI, 0.78-0.92, older age was associated with lower rates) were associated with higher rates of cCMV. In this meta-analysis, LMICs appeared to incur the most significant infection burden. Lower rates of cCMV were reported by studies using only blood or serum as a screening method.
Highlights
Human herpesvirus 5, cytomegalovirus (CMV), is a common cause of asymptomatic or mild illness in immunocompetent children and adults
The estimated pooled overall prevalence of congenital CMV (cCMV) was 0.67%
The pooled birth prevalence of cCMV was 3-fold greater in low- and middle-income countries (LMICs) (1.42%; 95% CI, 0.97%-2.08%; n = 23 studies) than in high-income countries (HICs) (0.48%; 95% CI, 0.40%-0.59%, n = 54 studies)
Summary
Human herpesvirus 5, cytomegalovirus (CMV), is a common cause of asymptomatic or mild illness in immunocompetent children and adults. Congenital CMV (cCMV) infection can lead to permanent sequelae in 15% to 18% of births, including death in 1%, neurocognitive sequelae in 5% to 15%, and hearing loss in 12% of individuals with cCMV.[1,2,3,4]. Studies have suggested that cCMV infection is a disease of disparity, with increased incidence, prevalence, and severity in low-income populations.[5,6,7,8] most studies that have been used to generate estimates of the burden of cCMV infection are from high-income countries (HICs).[5,9] the burden of cCMV infection is likely higher than currently available studies suggest. Congenital CMV is likely underreported worldwide owing to the lack of available testing in low- and middle-income countries (LMICs) and lack of systematic testing in countries of all income levels
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